Growth and differentiation factor 3/Vg-1-related protein (GDF-3/Vgr-2), activin BA and activin BB are members of the transforming growth factor beta superfamily. Members of this superfamily play important roles in a variety of developmental processes. In an effort to aid in the characterization of proteins from this superfamily, the candidate intends to study the functions of GDF-3/Vgr-2 and the activins using the following strategies: In phase I of this proposal the aims are: (1) To further characterize the GDF-3/Vgr-2 gene by studying the pattern of transcription from this gene, and to determine the conservation of this gene among species; (2) To analyze the expression pattern of GDF-3/Vgr-2 mRNA in the developing mouse embryo and in adult mouse tissues by in situ hybridization; (3) To inactivate the GDF-3/Vgr-2 gene by homologous recombination in embryonic stem cells. (4) To substitute the activin BA mature region with activin BB to determine if these proteins are functionally interchangeable. In phase II of this proposal the aims are: (1) To continue to characterize the morphologic, histologic and biochemical characteristics of the mutant mice produced during phase 1; and (2) To crossbreed mice carrying a mutation in the GDF-3/Vgr-2 locus with other mice deficient in bone morphogenetic proteins and activins.